August 28, 2009

Human Y-chromosome mutation rate

(corrected)

This is a very important paper that showed that 4 base substitutions occurred a length of 10 million base pairs (or about 1/6th) of the Y chromosome in two individuals separated by 13 generations. What this means is:

Even when we are able to routinely sequence entire Y chromosomes, we will still not generally be able to tell apart fathers and sons as sons (via their Y chromosome) only sometimes have different Y chromosomes than their fathers. In a large number of cases there will be no mutations.

On the positive side, relationships in the entire human Y-chromosome phylogeny will be resolved with an accuracy of a few generations. We will no longer have to rely on poor resolution Y-STR "genetic distance" methods to determine relatedness of individuals. The chunky huge haplogroups dominating modern Y-chromosome pools will be resolved into a hierarchy of more exclusive families and really precise patterns of migration and admixture may be inferred.

UPDATE: It occurred to me that the new mutation rate could also be used to directly infer the age of Y-chromosome Adam -and other haplogroups-, using the SNP counting method of Karafet et al. One simply needs to find out how many bases were sequenced in that study to infer the expected number of mutations/generation.

Understanding the key process of human mutation is important for many aspects of medical genetics and human evolution. In the past, estimates of mutation rates have generally been inferred from phenotypic observations or comparisons of homologous sequences among closely related species [1,2,3]. Here, we apply new sequencing technology to measure directly one mutation rate, that of base substitutions on the human Y chromosome. The Y chromosomes of two individuals separated by 13 generations were flow sorted and sequenced by Illumina (Solexa) paired-end sequencing to an average depth of 11 or 20, respectively [4]. Candidate mutations were further examined by capillary sequencing in cell-line and blood DNA from the donors and additional family members. Twelve mutations were confirmed in 10.15 Mb; eight of these had occurred invitro and four invivo. The latter could be placed in different positions on the pedigree and led to a mutation-rate measurement of 3.0 108 mutations/nucleotide/generation (95% CI: 8.9 1097.0 108), consistent with estimates of 2.3 1086.3 108 mutations/nucleotide/generation for the same Y-chromosomal region from published human-chimpanzee comparisons [5] depending on the generation and split times assumed.

I wanted to say 1 mutation over 3,3 million bps, 0,3 over one million, but we know that Y hasn't an uniform mutation rate, then there will be region with an higher and others with a lower mutation rate. But probably, if I have right understood, not all mutations are fixed in the descendants, because, if they are detrimental, they bring to the death of that line.Anyway the SNPs tested by deCODEme and 23andME are very stable, as after thousands of years we have no mutations. There is something that doesn’t balance. Or, perhaps, that explains what we have already understood: that living persons are the few survived form much more who are deceased, and they are much more in the oldest clusters of an haplogroup. For this we find very few old cluster survived. The same happens with the oldest haplogroups, who have always less SNPs than the younger ones.Then our calculation, your calculation, must be thought again. This was, and will be, the enemy’s sorrow.

Said ad usum delphini: the SNPs that lack are the dark matter of the Universe, are the detrimental ones, and the lines survived are those that by chance have so far avoided those reefs.This till Y will survive.

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